Changes in the nutritional status of the body can have profound influences on the activity of the reproductive system. Chronic undernutrition is associated with delayed onset of puberty or the suppression of normal reproductive function in adults. The mechanisms by which chronic undernutrition leads to a decrease in the central drive to the reproductive axis is unknown. Our focus has been to develop a primate model in which short-term changes in food intake can be studied. We have shown that brief periods of fasting (i.e., one to two days) lead to a significant suppression of LH, FSH and testosterone secretion in adult male rhesus monkeys. Subsequent refeeding of monkeys after a brief period of fasting leads to a rapid and dramatic increase in LH and testosterone secretion within the first hour after meal intake. Our approach is to use the experimental paradigms of fasting and refeeding to identify neuronal systems which may mediate the changes in LH secretion caused by fasting and refeeding. We are focusing on three specific neuronal systems that may mediate nutrition induced changes in LH secretion a) the vagus nerves, b) noradrenergic pathways, and c) NPY containing neurons. To determine whether these or other central neural systems are activated by fasting and refeeding, we are using cFos expression as a marker of neuronal activation. Using in situ hybridization and immunocytochemical techniques, we are determining changes in gene expression in central neural systems that are activated. In the course of these studies, we have also identified metabolic hormones whose secretory patterns during fasting and refeeding change with the same time course as the changes in LH secretion. We are now focusing on the role of specific metabolic hormones, i.e., insulin and T3, in causing the suppression of LH secretion during fasting and the 640006ation of LH secretion during refeeding. These studies increase our understanding about metabolic/nutritional signals that occur during mild metabolic perturbations and thus are expected to provide information about the role that metabolic signals play in governing the normal pattern of LH and testosterone secretion in adulthood.